Nephritic and Nephrotic Syndromes

Question 1

Acute Postreptococcal Glomerulonephritis

Answer 1

NEPHRITIC
LM—glomeruli enlarged and hypercellular . IF—(“starry sky”) granular appearance
(“lumpy-bumpy”) due to IgG, IgM, and C3
deposition along GBM and mesangium. EM—subepithelial immune complex (IC)
humps.
Most frequently seen in children. Occurs
∼ 2 weeks after group A streptococcal infection of pharynx or skin. Resolves spontaneously. Type III hypersensitivity reaction.
Presents with peripheral and periorbital edema, cola-colored urine, hypertension.
anti-DNase B titers, complement levels.

Question 2

Rapidly progressive (crescentic) glomerulonephritis (RPGN)

Answer 2

NEPHRITIC
LM and IF—crescent moon shape C . Crescents consist of fibrin and plasma proteins (e.g., C3b) with glomerular parietal cells, monocytes, macrophages.
Several disease processes may result in this pattern, in particular:
Goodpasture Syndrome, Wegners, Microscopic Polyangiitis.
Poor prognosis

Question 3

Diffuse Proliferative Glomerulonephritis

Answer 3

NEPHRITIC
Due to SLE or membranoproliferative glomerulonephritis.
LM—“wire looping” of capillaries. EM—subendothelial and sometimes
intramembranous IgG-based ICs often with
C3 deposition. IF—granular.
Most common cause of death in SLE.
Can present as a nephrotic

Question 4

IgA Nephropathy (Berger Disease)

Answer 4

NEPHRITIC
LM—mesangial proliferation.
EM—mesangial IC deposits.
IF—IgA-based IC deposits in mesangium. Renal pathology of Henoch-Schönlein purpura
Often presents with renal insuf ciency or acute gastroenteritis. Episodic hematuria with RBC casts. Not to be confused with Buerger disease (thromboangiitis obliterans).

Question 5

Alport Syndrome

Answer 5

NEPHRITIC
Mutation in type IV collagen thinning and splitting of glomerular basement membrane. Most commonly X-linked.
Eye problems (e.g., retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness; “can’t see, can’t pee, can’t hear a buzzing bee.”
“Basket-weave” appearance on EM.

Question 6

Membranoproliferazive Glomerulonephritis (MPGN)

Answer 6

NEPHRITIC
Type I—subendothelial immune complex (IC) deposits with granular IF; “tram-track” appearance on PAS stain D and H&E stain
E due to GBM splitting caused by mesangial ingrowth.
Type II—intramembranous IC deposits; “dense deposits.”
MPGN is a nephritic syndrome that often copresents with nephrotic syndrome.
Type 1 may be 2° to hepatitis B or C infection. May also be idiopathic.
Type II is associated with C3 nephritic factor (stabilizes C3 convertase serum C3 levels).

Question 7

Focal Segmental Glomerulosclerosis

Answer 7

NEPHROTIC
LM—segmental sclerosis and hyalinosis A . IF—nonspeci c for focal deposits of IgM, C3,
C1.
EM—effacement of foot process similar to
minimal change disease.
Most common cause of nephrotic syndrome
in African Americans and Hispanics. Can
be 1° (idiopathic) or 2° to other conditions (e.g., HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, chronic kidney disease due to congenital malformations). 1° disease has inconsistent response to steroids. May progress to chronic renal disease.

Question 8

Minimal Change Disease (lipoid nephrosis)

Answer 8

NEPHROTIC
LM—normal glomeruli (lipid may be seen in PCT cells).
IF ⊝.
EM—effacement (fusion) of foot processes B due to loss of heparin sulfate . Most common cause of nephrotic syndrome
in children. Often 1° (idiopathic) and
may be triggered by recent infection, immunization, immune stimulus. Rarely, may be 2° to lymphoma (e.g., cytokine-mediated damage). 1° disease has excellent response to corticosteroids.

Question 9

Membranous Nephropathy

Answer 9

NEPHROPATHY
LM—diffuse capillary and GBM thickening C . IF—granular as a result of immune complex deposition. Nephrotic presentation of SLE.
EM—“spike and dome” appearance with subepithelial deposits.
Most common cause of 1° nephrotic syndrome in Caucasian adults. Can be 1° (idiopathic)
or 2° to other conditions (e.g., antibodies
to phospholipase A2 receptor, drugs [e.g., NSAIDs, penicillamine], infections [e.g., HBV, HCV], SLE, solid tumors). 1° disease has poor response to steroids. May progress to chronic renal disease.

Question 10

Amyloidosis

Answer 10

NEPHROTIC
LM—Congo red stain shows apple-green birefringence under polarized light.
Kidney is the most commonly involved organ (systemic amyloidosis). Associated with chronic conditions (e.g., multiple myeloma, TB, rheumatoid arthritis).

Question 11

Diabetic Glomerulonephropathy

Answer 11

NEPHROTIC
LM—mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions) D .
Nonenzymatic glycosylation of GBM permeability, thickening.
Nonenzymatic glycosylation of efferent arterioles GFR mesangial expansion.